State-of-the-art nanomechanical resonators are heralded as a central component for next-generation clocks, filters, resonant sensors, and quantum technologies. To practically build these technologies will require monolithic integration of microchips, resonators, and readout systems. While it is widely seen that mounting microchip substrates into a system can greatly impact the performance of high-Q resonators, a systematic study has remained elusive, owing to the variety of physical processes and factors that influence the dissipation. Here, we analytically analyze a mechanism by which substrates couple to resonators manufactured on them and experimentally demonstrate that this coupling can increase the mechanical dissipation of nanomechanical resonators when resonance frequencies of resonator and substrate coincide. More generally, we then show that a similar coupling mechanism can exist between two adjacent resonators. Since the substrate–mode coupling mechanism strongly depends on both the resonator position on the substrate and the mounting of the substrate, this work provides key design guidelines for high-precision nanomechanical technologies.